Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors.
Ether-á-go-go-1 (Eag1) is a CNS-localized voltage-gated potassium channel that is found ectopically expressed in a majority of extracranial solid tumors. While circumstantial evidence linking Eag1 to tumor biology has been well established, the mechanisms by which the channel contributes to tumor progression remain elusive. In this study, we have used in vivo and in vitro techniques to identify a candidate mechanism. A mutation that eliminates ion permeation fails to completely abolish xenograft tumor formation by transfected cells, indicating that Eag1 contributes to tumor progression independently of its primary function as an ion channel. Our data suggest that Eag1 interferes with the cellular mechanism for maintaining oxygen homeostasis, increasing HIF-1 activity, and thereby VEGF secretion and tumor vascularization.
Downie
Bryan R
BR
Max-Planck Institute of Experimental Medicine, Hermann-Rein Str. 3, 37075 Göttingen, Germany.
Sánchez
Araceli
A
Knötgen
Hendrik
H
Contreras-Jurado
Constanza
C
Gymnopoulos
Marco
M
Weber
Claudia
C
Stühmer
Walter
W
Pardo
Luis A
LA
D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D051638:Ether-A-Go-Go Potassium Channels / Q000096:biosynthesis* / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D051638:Ether-A-Go-Go Potassium Channels; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C496884:KCNH1 protein, human; C496885:Kcnh1 protein, mouse; D042461:Vascular Endothelial Growth Factor A